Post on 01-Dec-2018
Insuficiencia Cardíaca
Prof. Domingo A. Pascual Figal
Hospital Universitario Virgen de la Arrixaca
Facultad de Medicina, Murcia
Cambios en la Enfermedad Cardiovascular
en el último año
Implicaciones para la Práctica Clínica
2011 Top Game Changers in Cardiology:
………………………………
and the Top Game Changer Is...
Objetivo primario (Mortalidad CV u hospitalización por IC)
HR = 0,63 (IC 95% 0,54-0,74)
p < 0,001
100
0
60
50
40
30
20
10
0 1 2 3
Eplerenona
Placebo
Años desde la aleatorización
232 562 925 1.364 199 512 848 1.373
Mo
rtal
idad
CV
u h
osp
ital
izac
ión
po
r IC
(%
)
Eplerenona Placebo
Nº de pacientes en riesgo
Conclusiones
• En los pacientes con IC con disfunción sistólica y síntomas leves, la adición de eplerenona al tratamiento médico optimo:
– fue bien tolerada
– mejoró la supervivencia
– y previno hospitalizaciones
• NNT
– Objetivo primario, por año de seguimiento, es 19
– Para aplazar una muerte, por año de seguimiento, es 51
En el corto y
En el largo plazo
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Disposition of Patients
1373 Randomized to placebo
2737 Randomized
1364 Randomized to eplerenone
No AFF N= 911 (66.8%)
No AFF N= 883 (64.3%)
Median follow-up time 21 months,
AFF N= 453 (33.2%)
AFF N= 490 (35.7%)
No AFF N= 1794 (65.5%)
AFF N= 943 (34.5%)
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New Onset Atrial Fibrillation/Flutter (AFF)
0
2
4
6
8
10
0 1 2 3 4
New Onset AFF Cumulative Rate
(%)
Years from Randomization
Eplerenone
Placebo
No. at Risk
Placebo 883 611 345 133 1
Eplerenone 911 627 397 162 2
HR [95% CI] = 0.58 [0.35, 0.96]
P = 0.034
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Effects of eplerenone by baseline AFF:
without AFF
Total number of
subjects
Eplerenon
e
n = 911 (%)
Placebo
n = 883
(%)
Hazard
Ratio
P-value
Without AFF
CV death/HF
Hospitalization
160 (17.6%) 217 (24.6%) 0.70 <0.001
All-cause mortality or
HF hospitalization
175 (19.2%) 228 (25.8%) 0.72 0.001
All-cause
hospitalization
260 (28.5%) 294 (33.3%) 0.83 0.03
HF hospitalization 103 (11.3%) 150 (17.0%) 0.65 <0.001
All cause death or all
cause hospitalization
292 (32.1%) 341 (38.6%) 0.81 <0.01
HF death or HF
hospitalization
107 (11.7%) 156 (17.7%) 0.65 <0.001
CV hospitalization 201 (22.1%) 244 (27.6%) 0.77 <0.01
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Effects of eplerenone by baseline AFF:
with AFF
Total number of
subjects
Eplerenon
e
N = 453
N (%)
Placebo
N = 490
N (%)
Hazard
Ratio
P-value P-value for
interaction
with/withou
t AFF
With AFF
CV death/HF
Hospitalization
89 (19.6%) 139 (28.4%) 0.60 <0.001 0.41
All-cause mortality or
HF hospitalization
95 (21.%) 148 (30.2%) 0.60 <0.001 0.28
All-cause
hospitalization
148 (32.7%) 197 (40.2%) 0.70 <0.01 0.22
HF hospitalization 61 (13.5%) 103 (21.0%) 0.56 <0.001 0.49
All cause death or all
cause hospitalization
170 (37.5%) 228 (46.5%) 0.70 <0.001 0.26
HF death or HF
hospitalization
63 (13.9%) 106 (21.6%) 0.56 <0.001 0.49
CV hospitalization
103 (22.7%) 155 (31.6%) 0.63 <0.001 0.20
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CV death or HF hospitalization by
baseline atrial fibrillation/flutter (AFF)
0
10
20
30
40
0 1 2 3 4
CV Death / HF Hospitalization
Cumulative Rate (%)
Years from Randomization
Without Baseline AFF
With Baseline AFF
No. at Risk
With AFF 943 602 385 161 2
Without AFF 1794 1171 689 270 4
HR [95% CI] = 1.13 [0.96, 1.33]
P = 0.153
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Study outcomes by baseline AFF
AFF
(N=943)
N (%)
No AFF
(N=1 794)
N (%)
P-value
HF Hospitalization/CV Death 228 (24.2%) 377 (21.0%) 0.153
HF Hospitalization
164 (17.4%) 253 (14.1%) 0.059
CV Death 122 (12.9%) 210 (11.7%) 0.643
All-cause mortality or heart
failure (HF) hospitalization
243 (25.8%) 403 (22.5%) 0.153
All-cause mortality 139 (14.7%) 245 (13.7%) 0.789
All-cause hospitalization 345 (36.6%) 554 (30.9%) 0.019
All cause death or all cause
hospitalization
398 (42.2%) 633 (35.3%) 0.008
HF death or HF hospitalization 169 (17.9%) 263 (14.7%) 0.067
CV hospitalization 258 (27.4%) 445 (24.8%) 0.355
¡HIPOTENSIÓN¡
HeartWare
HeartMate II
DOT-HF trial
SMART-AV
Study Design
Patient with Class II-IV symptoms, EF 40%, recent HF event
Randomization echocardiogram
Standard of Care
Minnesota Living With HF Questionnaire quarterly
Standard of Care + NT-proBNP
Minnesota Living With HF Questionnaire quarterly
Therapy adjusted to achieve optimal drug targets
Visits q3 months
Extra visits as needed for treatment goals
Therapy adjusted to achieve optimal drug targets PLUS NT-proBNP 1000 pg/mL
Visits q3 months
Extra visits as needed for treatment goals
Close-out echocardiogram
Total cardiovascular events assessed
NT-proBNP Concentrations
Baseline Follow-up P
Overall 2118 [1122-3831] 1321 [554-3197] .02
By treatment allocation
Treatment Baseline Follow-up P
SOC 1946 [951-3488] 1844 [583-3603] .61
NT-proBNP 2344 [1193-4381] 1125 [369-2537] .01
P = .03 for SOC follow-up versus NT-proBNP follow-up 44.3% of NT-proBNP subjects 1000 pg/mL
Primary Endpoint
0
20
40
60
80
100
120
Total CV Events
Nu
mb
er
of
even
ts
100 events
58 events
P =.009 SOC
NT-proBNP
*Logistic OddsNT-proBNP= 0.44
(95% CI= .22-.84; P =.019)
*Adjusted for age, LVEF, NYHA Class, and eGFR
Individual Endpoints
0
10
20
30
40
50
60
Worsening
HF
HF hosp ACS VT/VF CV death
Nu
mb
er
of
even
ts
P =.001
NB: 0 cerebral ischemia events in either arm
NB: 3 of 4 CV deaths in NT-proBNP arm
occurred after elective withdrawal from study
P =.002 P =.72 P =.41 P =.52
SOC
NT-proBNP
Age and outcomes
0
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
Age ≥ 75 years Age < 75 years
Mean
nu
mb
er
of
even
ts
SOC
NT-proBNP
P =.008 P =.005
*No interaction between age and NT-proBNP guided care was found (P =.11)
Safety
0
1
2
3
4
5
6
7
8
Acu
te re
nal fa
ilure
Diz
zines
s
Hyp
o/hyp
erka
lem
ia
Hyp
otensi
on
Synco
pe
Adverse event
% w
ith
even
ts
Acute
renal failure Dizziness
Hypo or
hyperkalemia Hypotension Syncope
Adverse events
P =.72 P =.70 P =.32 P =.08 P =.47
SOC
NT-proBNP
Minnesota Living with Heart
Failure Questionnaire
Variable SOC NT-proBNP P
Global Scale -5.0 [-18-0] -10.0 [IQR -17-7] .05
≥10 point 38.8% 61.2% .03
NT-proBNP patients had larger QOL improvements
than SOC, and were more likely to have large
(≥10 point) improvements in their MLWHF scores
Selected echo results
-20
-15
-10
-5
0
5
10
15
20
% c
han
ge
LVEF
Absolute
LVEF
Relative
LV end-systolic
volume index
LV end-diastolic
volume index
SOC (N= 56)
NT-proBNP (N=60)
P <.001 P =.008
P =.06 P =.01
sST2
Acute HF: Other Tools are Inadequate…
ST2 Most Predictive of Mortality
ST2 predicted mortality
better than other
demographic variables
and biomarkers
ST2 provides valuable
information not
available from existing
tools Hypertension, CAD,
Diabetes, Ejection Fraction,
and Smoking were not
significant predictors of
mortality, but were
evaluated.
72
Rehman S, et al.. Characteristics of the Novel Interleukin Family Biomarker ST2 in Patients with Acute Heart Failure. J. Am. Coll. Cardiol. 2008;52(18):1458-1465.
Januzzi JL Jr, et al. Importance of Biomarkers for Long-term Mortality Prediction in Acutely Dyspneic Patients. Clin Chem. 2010 Dec; 56(12):1814-21. Epub 2010 Oct 4.
*HR shown if p<.05; univariate HRs are given. ST2 HR is forST2>35 ng/mL from
PRIDE dataset; additional data provided by investigators to Critical Diagnostics.
For ST2 > median, HR is 2.85.
0
0,5
1
1,5
2
2,5
3
3,5
4
ST2 > 35ng/mL
NT-proBNP> median
BNP >median
PriorCongestive
HF
NYHASeverity
(perfunctional
class)
Age (peryear)
Hazard Ratio
ST2 in Acute Heart Failure
ST2 values associated with: – More symptomatic HF – Lower EF – Higher NP levels
Not affected by age, sex, BMI, etiology of HF, AF, anemia (unlike NP’s)1
Strong association between ST2 levels at presentation and 1-year mortality – Cut-point of 30 ng/ml
1Shah et al. Circ Heart Fail 2009
73
74
Isn’t an Earlier Signal By Definition A More Clinically Useful Signal?
Acute (Pooled Acute)
ST2 Give an Earlier Signal For
Short Term Adverse Events than NPs
ST2 Relationship to Time of All Cause Mortality
in Stable, Ambulatory HF Patients
75
Cumulative Adverse Event Rates ST2 Value >35 ng/ml
for Death, Transplant or Cardiovascular Hospitalization
76
ST2 Predicts Response to Aldosterone
Blockade
ST2 predicts which patients will
benefit most from aldosterone
blockade.
Eplerenone attenuates remodeling
more in patients with a higher
baseline ST2
ST2 not only predicts outcomes but
also predict which patients will
benefit most from intervention.
77
Weir AP, et al. J. Am. Coll. Cardiol. 2010;55;243-250.
High and low ST2 separated at median.
Implicaciones
• Incuestionable beneficio del bloqueo de la
aldosterona en pacientes con disfunción
sistólica.
• La reducción de la FC con ivabradina reduce
síntomas (estabilidad) y el remodelado
ventricular.
• El uso inicial de dosis altas de diuréticos en
bolos ev es seguro y puede mejorar la
evolución en pacientes con IC aguda
Implicaciones
• En pacientes con IC y FE preservada la
mejora sintomática debe ser el objetivo, sin
olvidar un enfoque periférico
• El beneficio de la resincronización queda
claro incluso en estadíos poco sintomáticos
o asintomáticos.
• La monitorización con dispositivos de
presión o de impedancia queda relegada,
mientras que la expansión de la asistencia
ventricular es imparable.